1. Field of the Invention
The present invention relates in general to a method for diagnosing a pervasive developmental disorder, for example, autism.
2. Background Art
Since the first clinical descriptions of autism in the 1940s, there has been no definite etiology or pathological finding leading to a cure or reversal of the condition. Recent reports suggest that there may be a combination of environmental or perhaps in utero risk factors, possible autoimmune risk factors, and perhaps localized inflammation of central nervous system neuroglia pointing to a compartmentalized central nervous system inflammatory response in at least some patients with autism.
Although no specific cell count elevation or direct central nervous system antibodies have been found, some recent studies of cytokines in the central nervous system may implicate an isolated response separate from the peripheral immune system.
These studies have not addressed direct neuroglial or innate central nervous system immune responses. The reports of elevated cytokines support possible increased tumor necrosis factor alpha (TNF-α) levels, in that interleukin-6 and elevated levels of TNF-receptor I antibodies have been reported in the cerebrospinal fluid of autistic patients. The role of TNF-α as a neuromodulating agent has been described in brain development as well, and it may play a role in neurons and neuroglial cells modulating glutaminergic transmission. Excessive glutamate excitotoxic effects acting on NMDA receptors could occur in the presence of excess TNF-α. This occurrence can lead to effects on microglial activation as well as other cytokines, such as nuclear factor-kappa-beta (NF-Kβ), among others. Such changes have also been seen in models of inflammation inducing epileptic activity in which neuroglial inflammation has caused epileptic spikes. Because of the high frequency of epileptic spikes seen in some subgroups of autistic children, and given that similar inflammatory mechanisms may play a role in spike formation, this finding may be more than a coincidence.
Vargas D L, et al. Neuroglial activation and neuroinflammation in the brain of patients with autism, Ann Neural 2005; 57:304 and Zimmerman A, et al. Cerebrospinal fluid and serum markers of inflammation in autism, Pediatr Neurol 2005; 35:195-201, disclose measuring cytokine profiles. However, neither article measures TNF-α, much less comparing the levels of TNF-α in cerebrospinal fluid and serum at the same time.
However, to the best of Applicant's knowledge, there are currently no known biological early diagnostic markers to identify at risk patients for a pervasive developmental disorder or to monitor treatment targets.